In a continuing effort to improve the subtype selectivity and agonist potency of estrogen receptor β (ERβ) ligands, we have designed and developed a thus far unexplored structural series obtained by molecular refinements of monoaryl-substituted salicylaldoximes (Salaldox B). The most interesting compounds in this series (2c, d) show remarkably high ERβ-binding affinities, with Ki values reaching the sub-nanomolar range (Ki=0.38 nM for 2c and 0.57 nM for 2d), and have very high levels of ERβ-subtype selectivity. Both compounds show a potent full agonist character on ERβ (EC50=0.23 nM for 2c and 1.3 nM for 2d). Furthermore, 2d shows a remarkable functional subtype selectivity, with a β/α transcription potency ratio 50-fold higher than that of estradiol.

Selective and potent agonists for estrogen receptor beta derived from molecular refinements of salicylaldoximes

BERTINI, SIMONE;GRANCHI, CARLOTTA;TUCCINARDI, TIZIANO;MARTINELLI, ADRIANO;MACCHIA, MARCO;MINUTOLO, FILIPPO
2011

Abstract

In a continuing effort to improve the subtype selectivity and agonist potency of estrogen receptor β (ERβ) ligands, we have designed and developed a thus far unexplored structural series obtained by molecular refinements of monoaryl-substituted salicylaldoximes (Salaldox B). The most interesting compounds in this series (2c, d) show remarkably high ERβ-binding affinities, with Ki values reaching the sub-nanomolar range (Ki=0.38 nM for 2c and 0.57 nM for 2d), and have very high levels of ERβ-subtype selectivity. Both compounds show a potent full agonist character on ERβ (EC50=0.23 nM for 2c and 1.3 nM for 2d). Furthermore, 2d shows a remarkable functional subtype selectivity, with a β/α transcription potency ratio 50-fold higher than that of estradiol.
Bertini, Simone; A., DE CUPERTINIS; Granchi, Carlotta; B., Bargagli; Tuccinardi, Tiziano; Martinelli, Adriano; Macchia, Marco; J. R., Gunther; K. E., Carlson; J. A., Katzenellenbogen; Minutolo, Filippo
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11568/199936
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